The present invention generally relates to the field of diagnostic spectroscopy, and more specifically, to an optical sampling subsystem that reduces the spectral complexity of light exiting a heterogeneous sample and collected by a plurality of fiber optics. The present invention increases the signal-to-noise ratio while compensating for spectral consistency and quantitative performance by providing means for creating a generally uniform radiance at the input of a wavelength dispersive or modulating device.
Spectral data arising from spectroscopic analysis provides practitioners with a wealth of detailed information about the identity, structure, concentration or constituents of samples. Spectral data derives from the detected and recorded energy change of a molecule through the emission or absorption of a photon.
In particular, practitioners focus upon a molecule""s vibration. Atoms within a molecular species vibrate back and forth about an average distance. Absorption of light by an atom at an appropriate energy causes the atoms to become excited, elevating the atom to a higher vibration level. The excitation of the atoms to an excited state occurs only at certain discrete energy levels, which are characteristic for that particular molecule. Infrared absorption spectroscopy is particularly useful for performing this type of analysis. In absorption spectroscopy, the net absorption of incident radiation at various wavelengths is measured.
Radiation passing through a sample is attenuated depending upon the pathlength traveled by the radiation and the strength of absorptions at various individual wavelengths for constituents within that particular sample. Recording and mapping the relative strength of the absorption versus wavelength results in a unique. absorption xe2x80x9cfingerprintxe2x80x9d for that particular sample.
One application area for multivariate quantitative spectroscopy is the measurement of tissue attributes or analytes noninvasively. A specific application is the measurement of glucose noninvasively for subjects with diabetes or subjects to be screened for diabetes. Other analytes or attributes of tissue can be measured such as alcohol, urea or the presence of cancer-related abnormalities. All of these applications are difficult due to the complexity of the tissue, a turbid media, and the small size of the analyte or attribute signal. For the measurement of analytes with small concentrations in turbid media, spectroscopic variances that overlap with the absorbance spectrum of the analyte of interest or give the appearance of absorbance at a critical wavenumber have been found to significantly affect the measurement. Spectroscopic interferences can include any spectroscopic variances unrelated to the analyte of interest but present during calibration development or during the measurement. Spectral interferences that overlap with or appear similar to the analyte of interest by showing variation in absorbance at a critical wavenumber, that is not actually due to variation in the analyte or attribute, lead to decreased accuracy of measurement.
In any spectroscopic system, a sampling subsystem must be utilized to introduce light into the sample under analysis, such as tissue, and to collect at least a portion of the light that is not absorbed by the sample to direct this diffusely reflected light to a spectrometer for analysis. The design of the sampling subsystem has been found to introduce variance in the analysis that is not associated with the analyte or attribute under analysis. To achieve accurate analysis, sampling subsystem variances must be reduced or a chemometric model that is insensitive to these variances must be developed. Modeling for sampling subsystem variances increases the complexity of any model, and therefore it is preferred to reduce or eliminate the effects of as many sampling subsystem variances as possible. As disclosed herein, the present invention includes a sampling subsystem design that reduces or eliminates the effects of sampling subsystem variance by reducing the complexity of the spectral analysis of the non-absorbed light collected from a sample after interaction therewith.
The present invention is directed to an optical sampling subsystem, preferably used for optically sampling tissue. The purpose of the subsystem is to introduce radiation generated by an illumination subsystem into the tissue of a subject or other sample and to collect at least a portion of the light or radiation that has interacted with the tissue or sample and has not been absorbed by the tissue. The subsystem transmits that light or radiation to a spectrometer subsystem for measurement. In particular, the optical sampling subsystem of the present invention reduces the effect of variances introduced by the optical subsystem which would result in less accurate analyte measurement or a more complex model to account for such variances. In preferred embodiments, the optical subsystem reduces spectral complexity of the light exiting the heterogeneous sample and collected by a plurality of optical fibers. The invention, in preferred embodiments, includes means for creating a generally uniform radiance at the input of a wavelength dispersive or modulating device within the spectrometer subsystem.
The means for creating a generally uniform radiance at the input of the wavelength dispersive or modulating device is preferably a radiation homogenizer which is used in combination with preferred optical inputs and optical outputs. A preferred optical ouput includes a plurality of optical fibers bundled in a spaced geometric pattern that collects the most light possible from the illumination subsystem after sample interaction in order to maximize the signal-to-noise ratio achieved by the subsystem. The combination of optical input and optical output devices disclosed herein and the means for creating a generally uniform radiance at the input of the wavelength dispersive or modulating device reduces the spectral complexity arising from photometric errors introduced by the heterogeneous sample and also reduces instrument dependent X-axis shift in order to reduce the complexity of the spectra analyzed by the multivariate calibration model used to determine a property or analyte concentration.
In preferred embodiments of the present invention, the sampling subsystem is incorporated into a spectroscopic system for determining a property of a heterogeneous sample. The apparatus preferably includes a light source that generates light with the light source optically coupled to a sampling means for transmitting at least a portion of the generated light to tissue and collecting at least a portion of the light modified by interaction with the tissue. The sampling means preferably includes a sample head for receiving a sample and a plurality of receiver optical fibers which have input ends and output ends. The input ends are disposed in the sample head for collecting at least a portion of the light modified by the tissue, while the output ends are optically coupled to an input end of a radiation homogenizer. The output from the radiation homogenizer is transferred to a spectrometer through optical coupling with the output end of the receiver optical fibers. The spectrometer includes means for processing the optical information to determine a property of the sample.
In preferred embodiments, the illumination subsystem generates near-infrared light including at least one wavelength indicative of the property of interest in human tissue. The spectrometer is preferably an FTIR spectrometer and further preferably includes a data acquisition subsystem which receives the electrical representation of the interferogram from the FTIR spectrometer. The data acquisition subsystem preferably includes means for amplifying and filtering the electrical representation and converting a resulting electrical signal to its digital representation. Finally, the system preferably includes a computing subsystem for receiving the digital representation which further includes a multivariate algorithm for calculating the property in human tissue.
In a preferred method for spectroscopic analysis, the above system is provided and radiation is emitted from the radiation source emitter and illuminates the sample with such radiation. At least a portion of the radiation is collected after interaction with the sample by a plurality of optical fibers. The output from the optical fibers is then homogenized with subsequent transfer to a spectrometer and detector for measuring the analyte concentration within the sample source.